Re-emergent Tremor Research Articles

Early re-emerging tremor after MRgFUS thalamotomy: case-control analysis of procedural and imaging features.

This study aimed to identify possible prognostic factors determining early tremor relapse after Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) thalamotomy in patients with essential tremor (ET) and Parkinson's disease (PD). Nine patients (six ET and three PD) who underwent Vim MRgFUS thalamotomy in a single institution and developed early re-emergent tremor were analyzed. A control group of patients matched pairwise for sex, pathology, age, disease duration, and skull density ratio (SDR) was selected to compare the technical-procedural data and MR imaging evidence. MR imaging findings compared between groups included lesion shape and volume in multiparametric sequences, as well as Fractiona Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) values derived from Diffusion Tensor Imaging Diffusion Weighted Imaging (DTI) and Diffusion Weighted Imaging (DWI) sequences. We did not find statistically significant differences in gender and age between the two groups. Technical and procedural parameters were also similar in both treatment groups. In MRI analysis, we found lesions of similar size but with greater caudal extension in the control group with stable outcomes compared to patients with tremor relapse. In our analysis of early recurrences after thalamotomy with focused ultrasound, there were neither technical and procedural differences nor prognostic factors related to lesion size or ablation temperatures. Greater caudal extension of the lesion in patients without recurrence might suggest the importance of spatial consolidation during treatment.

Re-emergent Tremor in Parkinson's Disease: Evidence of Pathologic β and Prokinetic γ Activity.

Re-emergent tremor is characterized as a continuation of resting tremor and is often highly therapy refractory. This study examines variations in brain activity and oscillatory responses between resting and re-emergent tremors in Parkinson's disease. Forty patients with Parkinson's disease (25 males, mean age, 66.78 ± 5.03 years) and 40 age- and sex-matched healthy controls were included in the study. Electroencephalogram and electromyography signals were simultaneously recorded during resting and re-emergent tremors in levodopa on and off states for patients and mimicked by healthy controls. Brain activity was localized using the beamforming technique, and information flow between sources was estimated using effective connectivity. Cross-frequency coupling was used to assess neuronal oscillations between tremor frequency and canonical frequency oscillations. During levodopa on, differences in brain activity were observed in the premotor cortex and cerebellum in both the patient and control groups. However, Parkinson's disease patients also exhibited additional activity in the primary sensorimotor cortex. On withdrawal of levodopa, different source patterns were observed in the supplementary motor area and basal ganglia area. Additionally, levodopa was found to suppress the strength of connectivity (P < 0.001) between the identified sources and influence the tremor frequency-related coupling, leading to a decrease in β (P < 0.001) and an increase in γ frequency coupling (P < 0.001). Distinct variations in cortical-subcortical brain activity are evident in tremor phenotypes. The primary sensorimotor cortex plays a crucial role in the generation of re-emergent tremor. Moreover, oscillatory neuronal responses in pathological β and prokinetic γ activity are specific to tremor phenotypes. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Persistence of Basal Ganglia Oscillatory Activity During Tremor Attenuation by Movement in Parkinson's Disease Patients.

One of the characteristics of parkinsonian tremor is that its amplitude decreases with movement. Current models suggest an interaction between basal ganglia (BG) and cerebello-thalamo-cortical circuits in parkinsonian tremor pathophysiology. We aimed to correlate central oscillation in the BG with electromyographic activity during re-emergent tremor in order to detect changes in BG oscillatory activity when tremor is attenuated by movement. We performed a prospective, observational study on consecutive parkinsonian patients who underwent deep brain stimulation surgery and presented re-emergent tremor. Coherence analysis between subthalamic nucleus/globus pallidus internus (STN/GPi) tremorous activity measured by microrecording (MER) and electromyogram (EMG) from flexor and extensor wrist muscles during rest, posture, and re-emergent tremor pause was performed during surgery. The statistical significance level of the MER-EMG coherence was determined using surrogate data analysis, and the directionality of information transfer between BG and muscle was performed using entropy transfer analysis. We analyzed 148 MERs with tremor-like activity from 6 patients which were evaluated against the simultaneous EMGs, resulting in 296 correlations. Of these, 26 presented a significant level of coherence at tremor frequency, throughout rest and posture, with a complete EMG stop in between. During the pause, all recordings showed sustained MER peaks at tremor frequency (±1.5 Hz). Information flows preferentially from BG to muscle during rest and posture, with a loss of directionality during the pause. Our results suggest that oscillatory activity in STN/GPi functionally linked to tremor sustains firing frequency during re-emergent tremor pause, thus suggesting no direct role of the BG circuit on tremor attenuation due to voluntary movements. © 2024 International Parkinson and Movement Disorder Society.

Distal Upper Limb Tremor during Walking in Parkinson's Disease.

Distal upper limb tremor during walking (TW) is frequently observed in Parkinson's disease (PD) but its clinical features are unknown. To characterize the occurrence and the clinical features of TW in comparison to the other types of tremors in PD. Fifty-one PD patients with rest tremor were evaluated off- and on-treatment. Occurrence, body distribution, severity and latency of TW and of other tremor types were assessed. TW was present in 78% of the PD patients examined. TW body distribution and severity were similar to those of rest and re-emergent tremor but different from the postural tremor presented by the same patients. TW latency, observed in 85% of patients, was on average 5.8 s. Dopaminergic treatment significantly improved TW, rest, and re-emergent tremor severity but left TW latency unaffected. TW is a frequent motor sign in PD and is likely a clinical variant of rest tremor.

Connecting tremors - a circuits perspective.

Tremor is one of the most prevalent movement disorders in clinical practice. Here, we review new insights in the pathophysiology of tremor. We focus on the three most common tremor disorders: essential tremor (ET), dystonic tremor syndrome (DTS), and Parkinson's disease (PD) tremor. Converging evidence suggests that ET, DTS, and PD tremor are all associated with (partly) overlapping cerebral networks involving the basal ganglia and cerebello-thalamo-cortical circuit. Recent studies have assessed the role of these networks in tremor by measuring tremor-related activity and connectivity with electrophysiology and neuroimaging, and by perturbing network components using invasive and noninvasive brain stimulation. The cerebellum plays a more dominant and causal role in action tremors than in rest tremor, as exemplified by recent findings in ET, DTS, and re-emergent tremor in PD. Furthermore, the role of the cerebellum in DTS is related to clinical differences between patients, for example, whether or not the tremor occurs in a dystonic limb, and whether the tremor is jerky or sinusoidal. Insight into the pathophysiological mechanisms of tremor may provide a more direct window into mechanism-based treatment options than either the etiology or the clinical phenotype of a tremor syndrome.

Optimal Control Perspective on Parkinson's Disease: Increased Delay Between State Estimator and Controller Produces Tremor.

Parkinson's disease produces tremor in a large subset of patients despite generally inhibiting movement. The pathophysiology of parkinsonian tremor is unclear, leading to uncertainty in how and why treatments reduce tremor with varying effectiveness. Models for parkinsonian tremor attempt to explain the underlying principles of tremor generation in the central nervous system, often focusing on neural activity of specific substructures. In contrast, control system approaches to modeling the human motor system provide qualitative results that help inform conclusions from clinical studies. This article uses an optimal control approach to investigate the hypothesis that an increased delay in the central nervous system-unaccounted by delay compensation mechanisms-produces parkinsonian tremor. This hypothesis is motivated by the excessive inhibition projected from the basal ganglia to the thalamus in Parkinson's disease. The thalamus relays signals from the cerebellum to the primary motor cortex: previous mapping of optimal control components indicates this prospective delay exists between the estimator (cerebellum) and controller (primary motor cortex). Simulations demonstrate realistic tremor in a neuromuscular model of the wrist. In addition, changes to effort sensitivity in the optimal controller may account for some clinical features of parkinsonian tremor, including the characteristics of re-emergent tremor and the time-varying amplitude and frequency of tremor. Contextualization of the optimal control model with physiological models and clinical observations provides insight into the potential role of the basal ganglia and cerebello-thalamo-cortical circuit and how treatments like dopaminergic medications and deep brain stimulation reduce tremor.

Re-emergent Tremor in Parkinson's Disease: The Role of the Motor Cortex.

Parkinson's disease patients may show a tremor that appears after a variable delay while the arms are kept outstretched (re-emergent tremor). The objectives of this study were to investigate re-emergent tremor pathophysiology by studying the role of the primary motor cortex in this tremor and making a comparison with rest tremor. We enrolled 10 Parkinson's disease patients with both re-emergent and rest tremor. Tremor was assessed by spectral analysis, corticomuscular coherence and tremor-resetting produced by transcranial magnetic stimulation over the primary motor cortex. We also recorded transcranial magnetic stimulation-evoked potentials generated by motor cortex stimulation during rest tremor, tremor suppression during wrist extension, and re-emergent tremor. Spectral analysis, corticomuscular coherence, and tremor resetting were compared between re-emergent tremor and rest tremor. Re-emergent tremor showed significant corticomuscular coherence, causal relation between motor cortex activity and tremor muscle and tremor resetting. The P60 component of transcranial magnetic stimulation-evoked potentials reduced in amplitude during tremor suppression, recovered before re-emergent tremor, was facilitated at re-emergent tremor onset, and returned to values similar to those of rest tremor during re-emergent tremor. Compared with rest tremor, re-emergent tremor showed similar corticomuscular coherence and tremor resetting, but slightly higher frequency. Re-emergent tremor is causally related with the activity of the primary motor cortex, which is likely a convergence node in the network that generates re-emergent tremor. Re-emergent tremor and rest tremor share common pathophysiological mechanisms in which the motor cortex plays a crucial role. © 2020 International Parkinson and Movement Disorder Society.

Re-emergent tremor in patients with Parkinson’s disease: an imaging study

BACKGROUND AND PURPOSE: Re-emergent tremor (ReT) is the tremor that reappears after a variable period of latency while maintaining posture. Little is known about the mechanisms that contribute to the origin of this silent period (SP). Our aim was to compare the imaging characteristics of patients with and without ReT and find the structural correlate of SP if any. MATERIALS AND METHODS: Fifteen patients with ReT (Group 1) and eighteen patients without ReT (patients with rest tremor and postural tremor, but no latency) were evaluated clinically, electrophysiologically, with diffusion tensor imaging (DTI) and voxel-based morphometry (VBM). DTI parameters of different regions of interest were analyzed and compared with that of 37 healthy age- and gender-matched controls. RESULTS: No statistically significant difference was observed between the two groups in terms of age, duration of disease, levodopa equivalent dose, or severity of the disease. However, in the left supplementary motor area (SMA), there was a significant reduction of fractional anisotropy and an increase of radial diffusivity and mean diffusivity in patients with ReT (Group 1) as compared to patients without ReT (Group 2) and healthy controls. The results of the VBM analysis were not significant. CONCLUSION: The presence of abnormality of SMA suggests that patients with ReT have a different pathophysiological mechanism as compared to patients without ReT. This is a novel finding implicating a possible contribution of the frontal lobe to the genesis of SP in ReT. ReT could be a distinct clinical entity within the tremor dominant subtype.

Re-emergent tremor provocation

IntroductionRest and re-emergent tremor (RET) in Parkinson's disease (PD) are known to be markedly variable. The aim of this study is to evaluate the effect of tremor provocation on RET latency and variability. MethodsWe performed a prospective observational study in 21 PD patients with RET. Evaluations were conducted by accelerometric analysis of hand movements with and without provocation by counting out loud backwards from 100, in the OFF state. Differences in RET pause duration, tremor power at peak frequency, root mean square (RMS) and slope of return of the tremor after the pause was measured. Inter- and intra-subject variability were also calculated. ResultsRET pause duration showed a 75% decrease after provocation (p < 0.001), which led to zero in 52% of cases, as compared to 9% in unprovoked measurements (p < 0.001). Provocation also led to a 2.57 time increase in tremor power (p < 0.001), 1.37 time increase in RMS (p < 0.001) and 2.47 time increase in slope (p < 0.001). A significant decrease in inter-subject variability was also observed (p = 0.001). ConclusionTremor provocation led to RET amplitude increase, pause shortening, and variability decrease. Therefore, while provocation can be recommended for the evaluation of rest tremor in clinical practice, it might well annul its value for identifying the pause prior to re-emergent tremor.

Re-Emergent Kinetic Tremor in Parkinson’s Disease

BackgroundThis is a case of re-emergent kinetic tremor in Parkinson’s Disease (PD).Phenomenology shownThe video shows re-emergent kinetic tremor while drawing a spiral and with repeated attempts to drink water from a cup.Educational valueThe kinetic tremor described by patients with PD can be a re-emergent tremor which occurs after a few repetitive movements.

Re-Emergent Kinetic Tremor in Parkinson’s Disease

This is a case of re-emergent kinetic tremor in Parkinson's Disease (PD).The video shows re-emergent kinetic tremor while drawing a spiral and with repeated attempts to drink water from a cup.The kinetic tremor described by patients with PD can be a re-emergent tremor which occurs after a few repetitive movements.

035 Valproate-induced parkinsonism ‘an early warning’: case reports and review of literature

IntroductionWe describe two cases of valproate-induced parkinsonism, where the parkinsonian features develop after commencing valproate (VPA), in a time frame and manner well described by previous publications.1 In contrast to the published literature, that has short duration of follow-up, we have had a prolonged follow-up of these two cases, who initially improved on ceasing valproate, but then after a period progressed again, with the development of levodopa-responsive asymmetrical Parkinson’s disease.2Cases67 years old man, on VPA 500 mg twice a day for seizures since 2008, developed new rest, re-emergent left hand tremor and hypomimia in 2012. Within months, the parkinsonism progressed to decremental bradykinesia, cog-wheel rigidity and hypophonia. The symptoms initially improved with changing VPA to levetiracetam; however, the disease reappeared after 6 months and although levodopa-responsive, it has been progressive since then.88 years old man, on VPA 700 mg twice a day for seizures since 2010, developed upper limb decremental bradykinesia, cog-wheel rigidity, camptocormia and rest, re-emergent tremor in hands in 2011. The parkinsonism improved significantly with cessation of VPA; however, the disease re-emerged after 2 years and has been progressive since then.ConclusionVPA may be responsible for unmasking underlying subclinical parkinsonism and these patients represent an earlier onset of Parkinson’s disease related to VPA exposure, rather than a purely drug related parkinsonian dysfunction. These cases also highlight the importance of long-term follow up in VPA-induced parkinsonism. These observations are an important consideration for clinicians treating patients with parkinsonian features secondary to VPA exposure.ReferencesBrugger F, Bhatia KP, Besag FM. Valproate-associated parkinsonism: a critical review of the literature. CNS Drugs 2016;30(6):527–540.Mahmoud F, Tampi RR. Valproic acid-induced parkinsonism in the elderly: a comprehensive review of the literature. Am J Geriatr Pharmacother 2011;9(6):405–412.

Re-emergent Tongue Tremor in Neuroleptic-induced Parkinsonism

<strong>Background:</strong> A re-emergent tremor is suggested to be specific to Parkinson’s disease and although a tongue tremor has been reported in levosulpiride-induced parkinsonism (LIP), re-emergence has never been reported. <strong>Case Report:</strong> A 59-year-old female presented with a 3-month history of bradykinesia, 2-week history of right-leg tremor, and 10-day history of lip and tongue tremor. A review of the medication revealed a 15-month history of levosulpiride consumption. On examination, asymmetric bradykinesia, rigidity, rest tremor of the right leg, and re-emergent tongue tremor were observed. The parkinsonism subsided after levosulpiride was stopped. <strong>Discussion:</strong> This is the first report of re-emergent tongue tremor in LIP.

Latency of re-emergent tremor in Parkinson's disease is influenced by levodopa

IntroductionRe-emergent tremor (RET) is a common form of postural tremor observed in Parkinson's disease (PD) patients. Recent studies have shown that administration of levodopa decreases RET amplitude. However, drug effects on tremor pause duration are less clear. MethodsWe performed a prospective observational study in PD patients with RET, subjected to acute levodopa challenge. Tremor activity was measured during OFF and ON states both clinically, as well as by using accelerometers taped to the back of both hands. Correlation between RET amplitude and pause duration, as well with MDS-UPDRS scores were investigated. The slope of gradual increase of postural tremor after the pause was also measured in the OFF and ON states. ResultsSignificant inverse correlation between tremor amplitude and RET pause duration was observed in OFF (rs = −0.474, p = 0.030) and ON (rs = −0.569, p = 0.006) states. Levodopa reduced tremor amplitude (26%, p = 0.004) dampening slope gradient (22%, p = 0.029). Tremor pause duration also showed inverse correlation with postural tremor amplitude measured by MDS-UPDRS in OFF (rs = −0.311, p = 0.048) and ON (rs = −0.503, p = 0.020) states, as well as with total MDS-UPDRS Part III score (rs = −0.295, p = 0.009). Finally, accelerometric analysis proved to be more sensitive than visual inspection for detecting tremor pauses. ConclusionOur results suggest RET pause duration is amplitude related, since levodopa-induced amplitude decrease led to pause prolongation, associated with decreased tremor intensity and slope gradient dampening.

Editors' note: The nature of postural tremor in Parkinson disease

Using EMG of forearm muscles to study tremor, “The nature of postural tremor in Parkinson disease” suggested 2 distinct postural tremor phenotypes in Parkinson disease (PD), with different pathophysiology and treatment response. Reemergent tremor is a continuation of resting tremor during stable posturing, and it has a dopaminergic basis. Pure postural tremor is a less common type of tremor that is inherent to PD, but has a largely nondopaminergic basis. Commenting on the study, Dr. Jankovic points out that the latency between movement and the onset of the postural tremor is helpful to differentiate tremor in PD from other tremors. He also notes that sometimes tremor related to essential tremor and PD can coexist. He finally suggests that the lack of responsiveness of rest and reemergent tremor to dopaminergic drugs may be explained by involvement of nondopaminergic systems. In response, authors Dirkx et al. explain that, based on their study, reemergent tremor is fundamentally the same as resting tremor and that the latency between movement and tremor reemergence varies considerably. They add that pure postural tremor differs from reemergent tremor and agree that serotonergic (or noradrenergic, cholinergic) mechanisms may indeed play a role in pure postural tremor. Using EMG of forearm muscles to study tremor, “The nature of postural tremor in Parkinson disease” suggested 2 distinct postural tremor phenotypes in Parkinson disease (PD), with different pathophysiology and treatment response. Reemergent tremor is a continuation of resting tremor during stable posturing, and it has a dopaminergic basis.

Reader response: The nature of postural tremor in Parkinson disease

Dirkx et al.1 studied 73 patients with tremor-dominant Parkinson disease (PD) and recorded their tremor before and after levodopa using forearm EMG. They concluded that there were 2 types of postural tremor in these patients: reemergent tremor, noted in 81% of the patients, and pure postural tremor, present in 19%. They noted that reemergent tremor is a “continuation of resting tremor.” This confirms our report in which we coined the term “reemergent tremor” to draw attention to this type of postural tremor, often more troublesome in patients with PD than the typical rest tremor, and to differentiate it from essential tremor (ET).2

Author response: The nature of postural tremor in Parkinson disease.

We appreciate Dr. Jankovic's comments on our recently published article.1 Our findings suggest that reemergent tremor is fundamentally the same as resting tremor. In our cohort (n = 48), the average latency between movement and tremor reemergence was 15.9 seconds. The latency varied considerably (1 to >60 seconds) but was not associated with disease or tremor severity. Recent work suggests that reafference from voluntary movements may reset tremor,2 but other mechanisms may also apply.3

The patchy tremor landscape: recent advances in pathophysiology.

We focus on new insights in the pathophysiology of Parkinson's disease tremor, essential tremor, tremor in dystonia, and orthostatic tremor. Neuroimaging findings suggest that Parkinson's disease resting tremor is associated with dopaminergic dysfunction, serotonergic dysfunction, or both. Not all tremors in Parkinson's disease have the same pathophysiology: postural tremor in Parkinson's disease can be subdivided into pure postural tremor, which involves nondopaminergic mechanisms, and re-emergent tremor, which has a dopaminergic basis. Unlike Parkinson's disease tremor, essential tremor has an electrophysiological signature suggestive of a single (or several tightly coupled) oscillators. Visual feedback increases essential tremor and enhances cerebral activity in the cerebello-thalamo-cortical circuit, supplementary motor area, and parietal cortex. Little is known about dystonic tremor but the available evidence suggests that both the basal ganglia and the cerebellum play a role. Finally, recent work in orthostatic tremor points towards the role of the pontine tegmentum and dysfunctional cerebellar-SMA circuitry. Many pathological tremors involve the cerebello-thalamo-cortical circuitry, and the clinical and pathophysiological boundaries between tremor disorders are not always clear. Differences between tremor disorders - or even individual patients - may be explained by the specific balance of neurotransmitter degeneration, by distinct circuit dynamics, or by the role of regions interconnected to the cerebello-thalamo-cortical circuit.

Re-emergent tremor in Parkinson's disease: the effect of dopaminergic treatment.

Patients with Parkinson's disease (PD) with resting tremor may be affected by a tremor that appears after a varying latency while a posture is maintained, a phenomenon referred to as re-emergent tremor (RET). The aim of the study was to evaluate the occurrence and clinical features of RET in patients with PD tested off and on treatment, and to compare the effect of dopaminergic treatment on RET with the effect on resting and action tremor. We consecutively enrolled 100 patients with PD. Patients were clinically evaluated 24h after withdrawal of therapy (off-treatment phase) and 60min after therapy administration (on-treatment phase). We collected the demographic and clinical data of patients with PD. The severity of the disease was assessed by means of the Hoehn and Yahr scale and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III. We evaluated the latency, severity and body side affected both off and on treatment in patients with RET. Re-emergent tremor was present in 24% of the patients with PD off treatment and in 19% of the patients on treatment. Dopaminergic treatment reduced the clinical severity of RET. Dopaminergic treatment increased the number of patients with unilateral RET and reduced the number of those who had bilateral RET. RET and resting tremor responded similarly to dopaminergic treatment, whereas action tremor was less responsive. Patients with RET had milder motor symptoms than patients without RET both off and on treatment. Dopaminergic treatment modified RET occurrence, severity and body distribution. Dopaminergic depletion plays a role in the pathophysiology of RET.

The nature of postural tremor in Parkinson disease.

To disentangle the different forms of postural tremors in Parkinson disease (PD). In this combined observational and intervention study, we measured resting and postural tremor characteristics in 73 patients with tremulous PD by using EMG of forearm muscles. Patients were measured both "off" medication (overnight withdrawal) and after dispersible levodopa-benserazide 200/50 mg. We performed an automated 2-step cluster analysis on 3 postural tremor characteristics: the frequency difference with resting tremor, the degree of tremor suppression after posturing, and the dopamine response. The cluster analysis revealed 2 distinct postural tremor phenotypes: 81% had re-emergent tremor (amplitude suppression, frequency difference with resting tremor 0.4 Hz, clear dopamine response) and 19% had pure postural tremor (no amplitude suppression, frequency difference with resting tremor 3.5 Hz, no dopamine response). This finding was manually validated (accuracy of 93%). Pure postural tremor was not associated with clinical signs of essential tremor or dystonia, and it was not influenced by weighing. There are 2 distinct postural tremor phenotypes in PD, which have a different pathophysiology and require different treatment. Re-emergent tremor is a continuation of resting tremor during stable posturing, and it has a dopaminergic basis. Pure postural tremor is a less common type of tremor that is inherent to PD, but has a largely nondopaminergic basis.